Glutathione is a tripeptide comprising three amino acids, namely glutamic acid, cysteine and glycine, and is a major cysteine residue-containing compound in cells. As is known, glutathione plays various roles in cells, for instance contributing to radical scavenging, redox-mediated regulation of cell function, and detoxifying mechanisms, as well as serving as a SH-donor for various enzymes.
Decreases in the intra-cellular concentration of glutathione that plays these roles are known to give rise to conditions such as cell damage due to ultraviolet radiation exposure, inflammation, blackening, formation of freckles and blemishes, acute or chronic alcohol-derived liver damage, liver disease, chronic renal failure, lung diseases caused by smoking, idiopathic pulmonary fibrosis, cataracts, ischemic heart disease, Parkinson's disease, Alzheimer's disease, gastric ulcer, adult respiratory syndrome, immunodeficiency, bone-marrow aplasia, acquired immunodeficiency syndrome, latent viral infections, aging phenomena derived from physiological aging, as well as oncogenesis. Conventional approaches to treat conditions caused by low concentration of glutathione in cells have involved using glutathione formulations that contain glutathione, with a view to eliciting uptake of glutathione by cells having a lowered intracellular glutathione concentration (Patent Document 1). However, therapy relying on oral ingestion of glutathione formulations may fail to elicit the anticipated effects, depending on the affected area to be treated. Although arguably more effective than oral ingestion, therapies by intravenous injection of glutathione formulations were problematic in that, for instance, injection is painful, and requires hospital visits.
Therefore, an increase in the intracellular glutathione concentration through promotion of glutathione production of cells in vivo should conceivably allow increasing defenses against oxidative stress, which decline with age, suppressing damage from oxidative stress caused by ultraviolet radiation, and preventing, treating or improving various diseases that include, for instance, skin aging, pigmentation disorders such as blemishes, and preventing and/or treating various organ dysfunctions and various diseases caused by glutathione deficiency. Known extraction products based on the above concept and having glutathione production-enhancing activity include, for instance, bilberry extraction products and walnut extraction products (Patent document 2), and extraction products of plants of the genus Gardenia (Patent document 3).
Glutathione is present in the organism in the form of reduced glutathione, which has the effect of removing reactive oxygen species, and oxidized glutathione, which is formed through reaction of reduced glutathione and reactive oxygen species. In recent years it has been found that oxidized glutathione is a sleep-promoting substance that promotes sleep by inhibiting neuronal excitability. Therefore, promoting glutathione production and increasing intracellular concentration, not only of reduced glutathione but also of oxidized glutathione, should conceivably be effective for preventing, treating or improving sleep disorders such as insomnia. Known sleep-inducing agents based on this concept include agents using oxidized glutathione as an active ingredient (Patent document 4).
In living cells, γ-glutamylcysteine is biosynthesized through reaction of glutamic acid and cysteine, mediated by γ-glutamylcysteine synthetase. As is known, glutathione is biosynthesized through reaction of γ-glutamylcysteine and glycine, mediated by glutathione synthetase. Therefore, the glutathione concentration of cells in vivo could be conceivably increased by promoting the expression of γ-glutamylcysteine synthetase, which acts as a catalyst in the biosynthesis of γ-glutamylcysteine as the precursor of glutathione.
Patent document 1: WO 2003/032966
Patent document 2: JP 2006-241062 A
Patent document 3: JP 2006-347934 A
Patent document 4: JP 4-9336 A